Preliminary data from HIV-seropositive patients at Johns Hopkins demonstrate a high rate of death from lung cancer. We derived 87 cases of HIV-seropositive patients with lung cancer who had been treated at the institution. Almost all patients were young (median age 46 years), African-American males from inner city Baltimore with a strong history of cigarette smoking. The prevalence of smoking was 97%, with 89% being current smokers. Despite patients being carefully followed for their HIV disease, only 4.6% of the HIV-positive lung cancer patients initially presented with stage 1 disease, and only 11 patients (13%) were able to undergo surgery. Over the past 5 years, six large-scale computed tomography (CT) lung cancer screening trials of 18,387 patients at high risk for lung cancer have been published. Of 140 lung cancers detected, 79% (110/140) had stage 1 disease. This contrasts with 24% of patients presenting with stage 1 lung cancer patients without CT screening. This suggests that CT screening is sensitive in detecting small, early stage lung cancer. We hypothesize that CT screening of heavy HIV-seropositive smokers will detect a higher proportion of stage 1 lung cancers than are currently being detected. This project is a prospective cohort study that will enroll 200 HIV-seropositive smokers who have current or previous smoking history of at least 20 pack years. We anticipate 18 lung cancers in the first year alone. Specific aim 1 addresses if differences in stage distribution of HIV-positive patients at lung cancer diagnosis can be determined between those HIV-positive heavy smokers who are screened by spiral CT and historical controls. Our second specific aim focuses on the establishment of a specimen bank of serum, sputum, and tissue from these screened HIV-positive smokers. Our third specific aim is to use epigenetic analysis of sera and sputa collected in Specific Aim 2 as a complementary approach to low dose helical CT in order to discriminate radiologically indeterminate nodules as either molecularly positive or negative. [unreadable] [unreadable]